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Status: Bibliographieeintrag

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Verfasst von:Budczies, Jan [VerfasserIn]   i
 Gröschel, Stefan [VerfasserIn]   i
 Leichsenring, Jonas [VerfasserIn]   i
 Fröhling, Stefan [VerfasserIn]   i
 Schirmacher, Peter [VerfasserIn]   i
 Stenzinger, Albrecht [VerfasserIn]   i
Titel:Pan-cancer analysis of copy number changes in programmed death-ligand 1 (PD-L1, CD274)
Titelzusatz:associations with gene expression, mutational load, and survival
Verf.angabe:Jan Budczies, Michael Bockmayr, Carsten Denkert, Frederick Klauschen, Stefan Gröschel, Silvia Darb‐Esfahani, Nicole Pfarr, Jonas Leichsenring, Maristela L. Onozato, Jochen K. Lennerz, Manfred Dietel, Stefan Fröhling, Peter Schirmacher, A. John Iafrate, Wilko Weichert, and Albrecht Stenzinger
E-Jahr:2016
Jahr:August 2016
Umfang:14 S.
Fussnoten:Gesehen am 12.12.2018
Titel Quelle:Enthalten in: Genes, chromosomes & cancer
Ort Quelle:New York, NY : Wiley-Liss, 1989
Jahr Quelle:2016
Band/Heft Quelle:55(2016), 8, Seite 626-639
ISSN Quelle:1098-2264
Abstract:Inhibition of the PD-L1 (CD274) - PD-1 axis has emerged as a powerful cancer therapy that prevents evasion of tumor cells from the immune system. While immunohistochemical detection of PD-L1 was introduced as a predictive biomarker with variable power, much less is known about copy number alterations (CNA) affecting PD-L1 and their associations with expression levels, mutational load, and survival. To gain insight, we employed The Cancer Genome Atlas (TCGA) datasets to comprehensively analyze 22 major cancer types for PD-L1 CNAs. We observed a diverse landscape of PD-L1 CNAs, which affected focal regions, chromosome 9p or the entire chromosome 9. Deletions of PD-L1 were more frequent than gains (31% vs. 12%) with deletions being most prevalent in melanoma and non-small cell lung cancer. Copy number gains most frequently occurred in ovarian cancer, head and neck cancer, bladder cancer, cervical and endocervical cancer, sarcomas, and colorectal cancers. Fine-mapping of the genetic architecture revealed specific recurrently amplified and deleted core regions across cancers with putative biological and clinical consequences. PD-L1 CNAs correlated significantly with PD-L1 mRNA expression changes in many cancer types, and tumors with PD-L1 gains harbored significantly higher mutational load compared to non-amplified cases (median: 78 non-synonymous mutations vs. 40, P = 7.1e-69). Moreover, we observed that, in general, both PD-L1 amplifications and deletions were associated with dismal prognosis. In conclusion, PD-L1 CNAs, in particular PD-L1 copy number gains, represent frequent genetic alterations across many cancers, which influence PD-L1 expression levels, are associated with higher mutational loads, and may be exploitable as predictive biomarker for immunotherapy regimens. © 2016 Wiley Periodicals, Inc.
DOI:doi:10.1002/gcc.22365
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: http://dx.doi.org/10.1002/gcc.22365
 Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/gcc.22365
 DOI: https://doi.org/10.1002/gcc.22365
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1585130052
Verknüpfungen:→ Zeitschrift

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